This study will investigate the hypothesis that the endothelial lining of blood vessels plays a role in the effects of ethanol on vascular smooth muscle. These effects include a direct stimulation of vascular smooth muscle and an inhibition of contractions induced by other agonists. The study will also investigate the hypothesis that these effects of ethanol are the result of alterations in the movement of calcium across the muscle cell wall. The proposal includes the measurement of ethanol-induced contractions of rings of rat aorta and pulmonary vein. These rings, with and without endothelium, will be obtained from normal and tolerant animals. These same preparations would be used to study the inhibitory effect of ethanol on the contractions induced by norepinophrine, angiotesin II, KCl and CaCl2. Finally, the study proposes to use these tissue preparations measure calcium uptake stimulated by ethanol and the effect of ethanol on the uptake stimulated by norepinephrine, angiotensin II or KCl. The goal of this project is to develop a better understanding of the effects of ethanol on the cardiovascular system and of the mechanisms which might be involved in the development of tolerance to these effects following long term consumption of alcohol.